Longevity (ESHG 2008 abstracts)

European Human Genetics Conference (abstract database)

The relation of common diseases SNPs and life span: no evidence for shared genetic component
O. Y. Byichkova1, O. A. Makeeva1, I. V. Tsimbal'uk2, K. V. Puzyrev3, V. N. Maksimov4, V. P. Puzyrev1,2;
1Research Institute of Medical Genetics, Tomsk, Russian Federation, 2Siberian State Medical University, Tomsk, Russian Federation, 3Research Institute of Cardiology, Tomsk, Russian Federation, 4Research Institute of Therapy, Novosibirsk, Russian Federation.
Presentation Number: P07.028
Life span is a multifactorial trait with a strong genetic component. Besides the number of genes has been directly implicated into the processes of ageing and longevity, the genes responsible for common diseases such as cardiovascular (CVD) or immunity disorders are also had to be under intent consideration. The persistence and both elimination from human populations ‘predisposing’ common genetic variants is forced by a complex interplay of different evolutionary processes; some variants being unfavorable during particular periods of life can offer their owners advantages on the others. Latter should be taken into account e.g. while developing genetic test and interpreting frequently discrepant genetic data on disease association. Testing the hypothesis that CVD predisposing alleles can be related to the life span, we investigate several cohorts: healthy controls of childbearing age (aged from 20 to 45, n=282), nonagenarians (aged 90 and over, n=235) and patients with cardiovascular disease (arterial hypertension with different complications) (n=231) from the same geographic region and ethnicity (East Siberia, Russians) and genotyped for several well-known CVD candidate genes polymorphisms (G-308A TNF, C894T NOS3, and A1166C AGTR1). While all the three SNPs under study affected several important cardiovascular endophenotypes (arterial blood pressure measurements, cardiac parameters, left ventricular hypertrophy development est.) no significant differences had been revealed among nonagenarians and middle aged group. In this study we never found actual proof for the stated hypothesis, though a huge amount of other genetic variants and the larger samples are needed to be tested before its decline.

Age-dependent genetic polymorphism frequencies and Gene - Pass

V. S. Baranov1, H. V. Baranova2, O. S. Glotov1;
1Ott’s Institute of Obstetrics & Gynecology, St.Petersburg, Russian Federation, 2European Institute of Personalized Prevention, Nice, France.
Presentation Number: P07.058
The report highlights the results of collaborative studies of personalized anti-aging medicine and its impact into longevity and aging. Special attention is paid to the gene nets of cardiovascular diseases, renin-angiotensin system, diabetus mellitus, osteoporosis etc. Polymorphic variants of at least some particular genes such as ACE, AGT, PAII, MTHFR, APOE, also as metabolic genes, like GSTs and other oxidative stress markers (NOS) are considered as the most plausible candidates of the genes crucial for aging. Molecular analysis of these particular genes supplemented with relevant metabolic genes testing, responsible for efficiency of detoxification system might have substantial contribution into personalyzed anti - aging medicine. The data on allele frequencies distribution for 10 differenet genes in newborns (106), 119 middle age and 148 old people over 69 are presented Relevant gene testing supplemented with its adequate sophisticated interpretation and constructive recommendations might have substantial contribution to human health and should be considered as a new highly promising tool in anti-aging medicine “Gene - pass ” term is suggested for the individual DNA data bank reflecting increased personal susceptibility to these common disorders. Tremendous impact to its practical application could be achieved through wide scale application of biochip technology. The latter are already available or are in progress for a number of multifactorial diseases. Special attention is paid to Genetic Pass of Reproductive Health - a version of Genetic Pass adjusted to the needs of pregnant woman. Life in harmony with personal gene makeup remains indispensable prerequisite of longevity and good health..

Study on a possible effect of four longevity candidate genes (ACE, PON1, PPAR-gamma, APOE) on human fertility

R. M. Corbo1,2, L. Ulizzi1, L. Piombo1, R. Scacchi2;
1La Sapienza University, Rome, Italy, 2CNR Institute of Molecular Biology and Pathology, Rome, Italy.
Presentation Number: P07.080
A possible effect on fertility of four genes [angiotensin 1-converting enzyme (ACE), paraoxonase (PON1), peroxisome proliferator-activated receptor gamma (PPAR-g), and apolipoprotein E(APOE)] previously found associated with longevity was sought in order to determine whether they have a pleiotropic action at different life ages. The study population was 151 Italian subjects whose reproductive life took place at the beginning of the demographic transition (declining fertility and longer life expectancy) and who had produced a mean number of children (3.6±2.3) such as to be still useful to detect a differential reproductive efficiency associated with different genotypes.
Of these four longevity candidate genes, only PPAR-g and APOE appeared to have an effect on fertility, indicating their possible influence on reproductive efficiency. The PPAR-g Pro/Ala genotype, which in a previous study (Barbieri et el. 2004) showed a positive association with longevity only in men, was found associated with a higher number of children (6.1 ± 3.3) than Pro/Pro genotype (3.3 ± 1.9, p=0.001) only in men. Compared with the other APOE alleles, the APOE*2 allele, considered as an allele favouring a longer life-span, was confirmed to be associated with the lowest fertility (p=0.03). The logistic regression analysis indicated that APOE and PPAR-g polymorphisms act as independent determinants of reproductive efficiency. These data suggest that the APOE*2 allele may follow the model of antagonist pleiotropy, whereas the PPAR-g Pro/Ala genotype seems to exert beneficial effects both early in life and in advanced age in a gender-specific way.

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